Rodrigo Vitorio1, Samuel Stuart2, Andrew Giritharan1, Joseph Quinn1, John G Nutt1, Martina Mancini3. 1. Department of Neurology, Oregon Health & Science University, Portland, OR, United States. 2. Department of Neurology, Oregon Health & Science University, Portland, OR, United States; Department of Sport, Exercise and Rehabilitation, Northumbria University, Newcastle Upon Tyne, UK. 3. Department of Neurology, Oregon Health & Science University, Portland, OR, United States. Electronic address: mancinim@ohsu.edu.
Abstract
INTRODUCTION: Cholinergic dysfunction contributes to mobility deficits in Parkinson's disease (PD). People with PD rely on limited prefrontal executive-attentional resources for the control of locomotion, including turning. Cortical and behavioral responses to cholinergic augmentation during turning remains unclear. We examined prefrontal cortex (PFC) activity while turning-in-place and spatiotemporal measures of turns in response to usual dopaminergic medication and adjunct cholinergic augmentation. METHODS: This study consisted of a single-site, randomized, double-blind crossover trial. Twenty PD participants were assessed in the levodopa-off state and then randomized to either levodopa + donepezil (5 mg) or levodopa + placebo treatments for two weeks followed by a 2-week washout before crossover. The primary outcome was change from off state in PFC activity while turning-in-place (assessed with functional near-infrared spectroscopy). Secondary outcomes were changes in spatiotemporal turning measures (assessed with body-worn inertial measurement units) and accuracy in the secondary task. RESULTS: Nineteen participants completed the trial. While levodopa + placebo had no effect on PFC activity when turning-in-place with a dual-task, levodopa + donepezil led to a large reduction in PFC activity (effect size, -0.82). Spatiotemporal measures of turning improved with both treatments, with slightly greater effect sizes observed for levodopa + donepezil. Additionally, the accuracy in the concurrent cognitive task improved only with levodopa + donepezil (effect size, 0.63). CONCLUSION: The addition of cholinergic therapy with donepezil (5 mg/day for 2 weeks) to standard dopaminergic therapy reduced the burden on prefrontal executive-attentional resources while turning with a dual-task and improved secondary task accuracy and turning.
INTRODUCTION: Cholinergic dysfunction contributes to mobility deficits in Parkinson's disease (PD). People with PD rely on limited prefrontal executive-attentional resources for the control of locomotion, including turning. Cortical and behavioral responses to cholinergic augmentation during turning remains unclear. We examined prefrontal cortex (PFC) activity while turning-in-place and spatiotemporal measures of turns in response to usual dopaminergic medication and adjunct cholinergic augmentation. METHODS: This study consisted of a single-site, randomized, double-blind crossover trial. Twenty PD participants were assessed in the levodopa-off state and then randomized to either levodopa + donepezil (5 mg) or levodopa + placebo treatments for two weeks followed by a 2-week washout before crossover. The primary outcome was change from off state in PFC activity while turning-in-place (assessed with functional near-infrared spectroscopy). Secondary outcomes were changes in spatiotemporal turning measures (assessed with body-worn inertial measurement units) and accuracy in the secondary task. RESULTS: Nineteen participants completed the trial. While levodopa + placebo had no effect on PFC activity when turning-in-place with a dual-task, levodopa + donepezil led to a large reduction in PFC activity (effect size, -0.82). Spatiotemporal measures of turning improved with both treatments, with slightly greater effect sizes observed for levodopa + donepezil. Additionally, the accuracy in the concurrent cognitive task improved only with levodopa + donepezil (effect size, 0.63). CONCLUSION: The addition of cholinergic therapy with donepezil (5 mg/day for 2 weeks) to standard dopaminergic therapy reduced the burden on prefrontal executive-attentional resources while turning with a dual-task and improved secondary task accuracy and turning.
Authors: Roger L Albin; Martijn L T M Müller; Nicolaas I Bohnen; Cathie Spino; Martin Sarter; Robert A Koeppe; Ashley Szpara; Kamin Kim; Cindy Lustig; William T Dauer Journal: Ann Neurol Date: 2021-05-26 Impact factor: 11.274